Bourne Y, Watson M H, Hickey M J, Holmes W, Rocque W, Reed S I, Tainer J A
Department of Molecular Biology, Scripps Research Institute, La Jolla, California, 92037, USA.
Cell. 1996 Mar 22;84(6):863-74. doi: 10.1016/s0092-8674(00)81065-x.
The 2.6 Angstrom crystal structure for human cyclin-dependent kinase 2(CDK2) in complex with CksHs1, a human homolog of essential yeast cell cycle-regulatory proteins suc1 and Cks1, reveals that CksHs1 binds via all four beta strands to the kinase C-terminal lobe. This interface is biologically critical, based upon mutational analysis, but far from the CDK2 N-terminal lobe, cyclin, and regulatory phosphorylation sites. CDK2 binds the Cks single domain conformation and interacts with conserved hydrophobic residues plus His-60 and Glu-63 in their closed beta-hinge motif conformation. The beta hinge opening to form the Cks beta-interchanged dimer sterically precludes CDK2 binding, providing a possible mechanism regulating CDK2-Cks interactions. One face of the complex exposes the sequence-conserved phosphate-binding region on Cks and the ATP-binding site on CDK2, suggesting that CKs may target CDK2 to other phosphoproteins during the cell cycle.
人细胞周期蛋白依赖性激酶2（CDK2）与CksHs1（酵母细胞周期调控蛋白suc1和Cks1的人类同源物）复合物的2.6埃晶体结构显示，CksHs1通过所有四条β链与激酶C末端叶结合。基于突变分析，该界面在生物学上至关重要，但远离CDK2的N末端叶、细胞周期蛋白和调节性磷酸化位点。CDK2结合Cks单结构域构象，并与保守的疏水残基以及处于其封闭β铰链基序构象的His-60和Glu-63相互作用。β铰链打开形成Cksβ互换二聚体在空间上排除了CDK2的结合，提供了一种调节CDK2-Cks相互作用的可能机制。复合物的一个面暴露了Cks上序列保守的磷酸结合区域和CDK2上的ATP结合位点，这表明Cks可能在细胞周期中将CDK2靶向其他磷蛋白。
